Efficacy and safety of live attenuated persistent and rapidly cleared Mycobacterium tuberculosis vaccine candidates in non-human primates.
Efficacy and safety of live attenuated persistent and rapidly cleared Mycobacterium tuberculosis vaccine candidates in non-human primates.
复制标题
DOI：
10.1016/j.vaccine.2009.05.050
复制
发表时间：
2009-07-23
期刊：
影响因子：
5.5
通讯作者：
Jacobs WR Jr
中科院分区：
文献类型：
--
作者：
Larsen MH;Biermann K;Chen B;Hsu T;Sambandamurthy VK;Lackner AA;Aye PP;Didier P;Huang D;Shao L;Wei H;Letvin NL;Frothingham R;Haynes BF;Chen ZW;Jacobs WR Jr
结核病（TB）仍然是全球健康负担，需要安全的疫苗。BCG作为结核病疫苗具有局限性，因此我们将重点放在减毒活结核分枝杆菌突变体作为候选疫苗上。然而，在进行人体研究之前，有必要证明在非人灵长类动物（NHP）中的安全性。在这项研究中，我们评估了两种减毒活M。结核病双缺失疫苗株mc26020（ΔlysA ΔpanCD）和mc26030（ΔRD1 ΔpanCD）。在小鼠模型中，mc26020被迅速清除，而mc26030持续存在。mc26020和mc26030在食蟹猴中均安全且耐受性良好。在高剂量支气管内用强毒M.对于结核病，mc26020疫苗接种者的保护水平介于BCG疫苗接种和未接种之间。与生理盐水和mc26030疫苗接种组相比，BCG疫苗接种组的结核病相关病理学减少，临床评分改善，但各组之间的存活率没有差异。
Tuberculosis (TB) remains a global health burden for which safe vaccines are needed. BCG has limitations as a TB vaccine so we have focused on live attenuated Mycobacterium tuberculosis mutants as vaccine candidates. Prior to human studies, however, it is necessary to demonstrate safety in non-human primates (NHP). In this study, we evaluate the safety and efficacy of two live attenuated M. tuberculosis double deletion vaccine strains mc26020 (ΔlysA ΔpanCD) and mc26030 (ΔRD1 ΔpanCD) in cynomolgus macaques. In murine models, mc26020 is rapidly cleared while mc26030 persists. Both mc26020 and mc26030 were safe and well tolerated in cynomolgus macaques. Following a high-dose intrabronchial challenge with virulent M. tuberculosis, mc26020-vaccinates were afforded a level of protection intermediate between that elicited by BCG vaccination and no vaccination. BCG vaccinates had reduced tuberculosis-associated pathology and improved clinical scores as compared to saline and mc26030 vaccinates, but survival did not differ among the groups.
登录
查看更多内容
影响因子：
3.1
作者：
Sampson, SL;Dascher, CC;Hondalus, MK
通讯作者：
Hondalus, MK
影响因子：
5.5
作者：
Okada, Masaji;Kita, Yoko;Sakatani, Mitsunori
通讯作者：
Sakatani, Mitsunori
DOI：
10.1073/pnas.201404898
发表时间：
2001-09-25
影响因子：
11.1
作者：
Langermans, JAM;Andersen, P;Thomas, AW
通讯作者：
Thomas, AW
影响因子：
15.9
作者：
Hinchey, Joseph;Lee, Sunhee;Porcelli, Steven A.
通讯作者：
Porcelli, Steven A.
影响因子：
5.5
作者：
Waters, W. Ray;Palmer, Mitchell V.;Larsen, Michelle H.
通讯作者：
Larsen, Michelle H.